Folate Research Articles

Silk Fibroin-Based Lenvatinib Nanomedicine with Conformation Tunability for Systemic Treatment of Hepatocellular Carcinoma.

Multitarget tyrosine kinase inhibitors (TKIs) serve as first-line therapeutics in the systemic treatment of hepatocellular carcinoma (HCC), yet their clinical effectiveness is hampered by suboptimal pharmacokinetics and bioavailability. There is a critical need to enhance the circulation, tumor targeting, and infiltration of TKIs. In this context, we developed a silk fibroin (SF)-based nanomedicine that exploits the chemical versatility and conformation tunability of SF. Folic acid (FA) with affinity toward HCC cells is utilized to functionalize SF, simultaneously aiding in the pH-sensitive β-sheet transitions of SF. This dynamic conformation behavior is key to improving the nanomedicine's circulation, biological adhesion, and tumor localization. By encapsulating Lenvatinib (Leva) TKI, the nanomedicine exhibits tumor-targeted accumulation and potent inhibition on HCC cell survival and angiogenesis, thereby amplifying Leva's bioavailability and therapeutic impact. Owing to SF's low immunogenicity and high reproducibility, this SF-based approach for TKI delivery holds substantial promise for advancing HCC systemic therapy.

Beyond conventional therapy: Synthesis of multifunctional nanoparticles for rheumatoid arthritis therapy

Abstract Rheumatoid arthritis (RA) is a persistent inflammatory illness that causes joint destruction and dysfunction due to the activation of macrophages and the generation of reactive oxygen species. Current therapy choices frequently limit the effectiveness of targeting the inflammatory areas. To reduce inflammation and oxidative stress in RA, this research will create and assess multifunctional nanoparticles that selectively target inflammatory cells and deliver therapeutic medicines. Tannic acid, ferric chloride hexahydrate, methotrexate (MTX), and bovine serum albumin were conjugated using sonication and centrifugation to create the nanoparticles. Folic acid was added to improve the ability to target. Transmission electron microscopy, dynamic light scattering (DLS), UV-vis spectroscopy, and in vitro release experiments were used to characterize the nanoparticles. RAW 264.7 macrophage cells were used to test the cellular uptake of the nanoparticles using confocal microscopy and fluorescence-activated cell sorting (FACS). TFMBP-FA achieved 65.56%, and TFMBP reached 68.96%, indicating a high drug delivery rate for the synthesized nanoparticles. Confocal microscopy showed that the TFMBP-FA group had a greater density of fluorescent markers, indicating that the cells effectively targeted and absorbed the inflammatory environment. These results imply that the created nanoparticles may improve how medications are delivered during RA therapy.

Folic acid supplementation during fattening period affects growth and nutritional metabolism in Japanese Black beef cattle

The folate requirements for beef cattle have not been established. Therefore, we investigated whether rumen-unprotected folic acid supplementation during the fattening period affects carcass traits and nutritional metabolism in Japanese Black beef cattle. Eighteen Beef cattle aged 16 months were divided into three groups: control, low folic acid supplementation (0.43 g DM/day), and high folic acid supplementation (0.86 g DM/day). Treatment was administered for 12 months. Folic acid supplementation dose-dependently increased serum folate levels, suggesting that supplemental folic acid can be absorbed into the body. Folic acid supplementation dose-dependently decreased serum vitamin B12 levels, while plasma total homocysteine and methylmalonic acid levels—markers for deficiency of folate and/or vitamin B12—were unaffected. Thus, the treatment did not clearly affect the nutritional status of these vitamins. Supplementation increased body weight, with no negative effects on other carcass traits. The levels of insulin-like growth factor 1, retinol, albumin, and some amino acids in serum or plasma were affected by supplementation. These results suggest that rumen-unprotected folic acid supplementation during the fattening period could increase the body weight of Japanese Black beef cattle and the mechanism of action may be related to growth-related hormones and/or the metabolism of some nutrients, including folate.

Glycosyl Mobile Radical Structures of Folic Acid Receptors Impact the Internalization of Functionalized Folate Amphiphilic Alternating Copolymer in Cancer Cells

Folate receptor alpha (FRα) is a glycosylphosphatidylinositol (GPI) membrane-anchored protein containing three N-glycosylated residues at the N47, N139, and N179 termini. These glycosylation sites have been reported to be crucial for the receptor’s structural integrity and its ability to bind and internalize FA. Here, we investigated the role of FRα glycosylation in the binding and internalization efficacy of FA–DABA–SMA in pancreatic PANC-1 cancer cells. There is a strong association of the FA copolymer with FRα with a Pearson coefficient R-value of 0.7179. PANC-1 cancer cells were pretreated with maackia amurensis lectin II (MAL-2), sambucus Nigra lectin (SNA-1), peanut agglutinin (PNA), and wheat germ agglutinin lectin (WGA) at different doses followed by 20 kDa and 350 kDa FA–DABA–SMA loaded with coumarin 153 (C153). Increasing the dosage of MAL2, SNA-1, PNA, and WGA concomitantly and significantly increased the internalization of C153-loaded FA–DABA–SMA in the cells. The half maximal effective lectin concentrations (EC50) to induce cellular internalization into the cytoplasm of the lectins for MAL-2 were 35.88 µg/mL, 3.051 µg/mL for SNA-1, 7.883 µg/mL for PNA, and 0.898 µg/mL for WGA. Live cell imaging of the internalization of 20 kDa and 350 kDa FA copolymers indicated an aggregation of 350 kDa copolymer with FRα in the cytoplasm. In contrast, the 20 kDa FA copolymer remained in the membrane. The data indicate for the first time that the mobile positions of the glycosyl radical groups and the receptor tilt in generating steric hindrance impacted the individual FRα receptors in the binding and internalization of 350 kDa FA–DABA–SMA in cancer cells.

Influence of maternal health status during pregnancy and the child´s medical history on molar-incisor hypomineralization in a group of Spanish children (aged 6-14 years): a retrospective case-control study.

Molar-incisor hypomineralization (MIH) is a qualitative enamel defect that is highly prevalent in children. It has been reported that patients with MIH have higher caries occurrence with an increased need and frequency of dental treatment compared to patients without MIH. The objective of this study was to analyze the association between MIH and a series of factors related to maternal health status during pregnancy and children´s medical history in early childhood. A retrospective study of cases (patients with MIH) and controls (patients without MIH) was designed between 2023 and 2024. A total of 280 children (cases = 140; controls = 140) aged 6 to 14 years (138 boys and 142 girls) were examined according to the European Academy of Pediatric Dentistry (EAPD) criteria for MIH. A survey was carried out with mothers regarding the potential exposure of their children to etiological factors of MIH. Possible prenatal and postnatal etiological factors were obtained through a personal interview with the patients' mothers. The statistical analysis was carried out with the contrast test and the chi-square test. During pregnancy, folic acid consumption, alcohol intake, systemic viral and/or bacterial infections, and gestational diabetes were statistically significantly related to MIH, as were breastfeeding, asthma, and corticosteroid consumption during childhood. Although there are different factors that may have statistically significant relationships with MIH, they cannot be predicted. Therefore, longitudinal studies, with a large sample size, are needed to determine the influence of prenatal and postnatal factors on the prevalence and severity of MIH in children.

Clove Aqueous Extract Alleviates Acute Kidney Injury Induced by Folic Acid in Rats

Background: Acute Kidney Injury (AKI) is a common clinical disease that has a high incidence and mortality rate. Clove, a robust natural source of bioactive chemicals and rich in secondary metabolites, plays a wide range of biological roles. Aim: The present study aimed to assess the ameliorative efficacy of clove extract against acute renal damage induced by folic acid in rats. Methods: Gas Chromatography/Mass Spectrometry (GC/MS) was used to investigate the main components of clove extract. Folic acid, at a dose of 250 mg/kg, was delivered intraperitoneally to rats to induce AKI. Eighteen rats were divided into three groups: control, AKI, and AKI + clove extract (500 mg/kg). Results: The administration of clove extract significantly restored the levels of creatine, urea, uric acid, sodium, potassium, chloride, creatinine clearance, and microalbumin to nearly normal levels. Also, clove water extract inhibited oxidative stress by decreasing concentrations of Malondialdehyde (MDA) and Nitric Oxide (NO). Furthermore, clove extract elevated the levels of Glutathionereduced (GSH), Catalase (CAT), and Glutathione S-transferase (GST). Kidney section histology showed notable improvements after the administration of clove extract. Conclusion: The clove water extract has been found to contain many bioactive components possessing antioxidant and anti-inflammatory properties, effectively protecting against acute renal injury.

Characterization and monitoring of changes during lactation in the profile of multiple bioactive compounds of milk from grazing mares.

Mare milk has often been considered a food product with potential functional properties. However, the bioactive compound composition of mare milk, including vitamins and other minor bioactive compounds, as well as factors affecting this composition have scarcely been studied. Therefore, the present study aimed to characterize the changes during lactation in the content of water- and fat-soluble vitamins and total polyphenols, and the total antioxidant capacity of mare milk from semi-extensive farms. A total of 310 individual milk samples from 18 mares belonging to three commercial farms and 12 lactation times were analyzed. Ascorbic acid (vitamin C), thiamine (vitamin B1), riboflavin (vitamin B2), nicotinic acid and niacinamide (vitamins B3), pantothenic acid (vitamin B5), pyridoxal and pyridoxine (vitamins B6), folic acid (vitamin B9), cyanocobalamin (vitamin B12), tocopherols and tocotrienols (vitamin E) and retinol and retinyl esters (vitamin A) were quantified using liquid chromatography. Total polyphenols and antioxidant capacity assays were analyzed using spectrophotometry. The concentration of most bioactive compounds tended to decline as lactation progressed, with the exception of polyphenols and the total antioxidant capacity that oscillated during lactation. On the other hand, the effect of the different semi-extensive management of the farms was only significant for vitamin B3 content. To the best of our knowledge, the present study provides the most in-depth description of the vitamin profile of mare milk as well as new insights into polyphenol content and antioxidant capacity of mare milk. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Folic acid-targeted redox responsive polylactic acid-based nanoparticles co-delivering pirarubicin and salinomycin suppress breast cancer tumor growth in vivo.

Targeted cancer therapy using nanocarriers has emerged as a promising solution to the majority of drawbacks associated with conventional chemotherapy. The present research work describes the development of folic acid (FA)-targeted redox responsive [S-(PLA-b-PEG-CONH)]2 polymeric nanoparticles for the co-delivery of pirarubicin (Pira) and salinomycin (Sal). The nanoparticles' redox responsiveness arises from embedded disulfide bonds within the polymer, which gradually break in response to high GSH levels in tumors, enabling sustained drug release. The nanoparticles exhibited a hydrodynamic size of ∼104 nm and a surface charge density of -15.5 mV with low PDI values. Blank nanoparticles (w/o drug) showed negligible toxicity towards both non-malignant human and murine cells and exhibited excellent stability under different environmental conditions for up to 3 weeks. A cellular internalization study conducted using Rho B/C6 dual-dye-encapsulated nanoparticles showed efficient uptake of the nanoparticles after just 1 hour of incubation with SUM-149 2D adherent cells and 3D spheroids. The release of Pira and Sal from Pira/Sal dual-loaded nanoparticles increased significantly in a reducing environment. The % cumulative release of Pira increased from 20.5% ± 1.0 in PBS (pH 7.4) to 40.1% ± 0.4 in dithiothreitol (DTT) after 20 days; similarly, the % cumulative release of Sal increased from 36.2% ± 1.7 in PBS (pH 7.4) to 51.5% ± 1.7 in DTT. The cytotoxicity studies of FA-targeted Pira/Sal dual-loaded nanoparticles with varying Pira : Sal ratios (1 : 1, 3 : 1 and 1 : 3) revealed that the nanoparticles displayed 8-10 fold lower IC50 values than the respective free drug formulations across multiple breast cancer cell lines including SUM-149, MDA-MB-231 and EAC as well as in 3D mammospheres. Balb/c syngeneic mice bearing EAC tumors experienced ∼100% tumor regression upon treatment with FA-targeted Pira/Sal (3 : 1) dual-loaded nanoparticles, indicating synergistic anti-tumor potency. In vivo survival and histopathological studies indicated no significant toxicity in vital organs of the body as compared to free drugs. Based on the performance, the currently investigated FA-targeted Pira/Sal dual-loaded nano-formulation is recommended to be further explored in other cancer types as well as in higher animals for cancer therapy.

Comparative Analysis of Vitamin D, Folic Acid, and Antioxidant Minerals in Various Stages of Lung Cancer

Comparative Analysis of Vitamin D, Folic Acid, and Antioxidant Minerals in Various Stages of Lung Cancer

Fluorescent “On‐off‐on” Probe for Cascade Detection of Ag(I) and Ascorbic Acid Using Folic Acid Protected Copper Nanoclusters

Folic acid (FA) protected copper nanoclusters (FA‐CuNCs, λex = 350 nm, λem = 445 nm) were synthesized and used as a fluorescent "on‐off‐on" probe for the cascade detection of Ag+ and ascorbic acid (AA). The fluorescence emission of FA‐CuNCs at 445 nm was quenched significantly by Ag+ due to the analyte‐induced aggregation followed by the formation of larger nanoparticles. However, when AA was added to the in‐situ generated Ag@FA‐CuNCs, the fluorescence emission of FA‐CuNCs was recovered at 445 nm because of the AA‐directed reduction of Ag+ to Ag0. The experimental conditions, such as pH, incubation time, and quencher Ag+ concentrations, were optimized to achieve improved sensitivity. The detection limit for Ag+ and AA was estimated as 37.1 nM and 0.27 µM with a linearity range of 2.49‐22 µM and 4.71‐81.53 µM, respectively. In real sample analysis, the recoveries of Ag+ ions in river water and AA in orange juice samples were found between 99‐93% and 97‐94% using the probes FA‐CuNCs and Ag@FA‐CuNCs, respectively. Overall, this work offers a viable method for the sequential detection of Ag+ and AA using FA‐CuNCs via a fluorescence “on‐off‐on” switch mechanism.

Maternal Dietary Deficiencies in Folic Acid and Choline Change Metabolites Levels in Offspring after Ischemic Stroke.

Background/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. Methods: A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies. Results: At 1-week post-stroke, female offspring from the FADD group showed the greatest number of altered metabolites, including pathways involved in cholesterol metabolism and neuroprotection. At 4 weeks post-stroke, both FADD and ChDD groups exhibited significant disruptions in metabolites linked to inflammation, oxidative stress, and neurotransmission. Conclusions: These alterations were more pronounced in females compared to males, suggesting sex-dependent responses to maternal dietary deficiencies. The practical implications of these findings suggest that ensuring adequate maternal nutrition during pregnancy may be crucial for reducing stroke susceptibility and improving post-stroke recovery in offspring. Nutritional supplementation strategies targeting folic acid and choline intake could potentially mitigate the long-term adverse effects on metabolic pathways and promote better neurological outcomes. Future research should explore these dietary interventions in clinical settings to develop comprehensive guidelines for maternal nutrition and stroke prevention.

Exploring the significance of Ranjaka Pitta in the formation of Rakta Dhatu with respect to Erythropoiesis

ABSTRACT The body's foundational basis lies in the trinity of Dosha [bio-energy principles], Dhatu [structural components of body], and Mala [waste]. The body comprises of three Dosha, Pitta being one of them. Due to its Ushna [hot] Guna [attribute/quality], Pitta plays a crucial role in Pachana [digestion or biotic transformation]. Pitta Dosha is divided into five subtypes based on both their location and function. Amongst these, Ranjaka [coloring] Pitta is involved in the formation of Rakta [blood] Dhatu. Ayurvedic texts indicate Yakrit [liver], Pleeha [spleen], and Amashaya [stomach] as the locations of Ranjaka Pitta, emphasizing its synergy with Raktagni [transformation factors] in the intricate formation of Rakta Dhatu. The Liver, Spleen, and Bone Marrow are vital for Erythropoiesis in modern science. The liver stores essential nutrients like vitamin B12, folic acid, and iron. Vitamin B12 is critical for erythropoiesis (the process of origin, development and maturation of erythrocytes) and the intrinsic factor secreted by the stomach's parietal cells plays a key role in its absorption. There are similarities in the Ayurvedic & Modern processes. In this article, we explore the role of Ranjaka Pitta in Rakta Dhatu formation, bridging Ayurvedic insights with modern medical science for a comprehensive understanding.

Myeloid neoplasm with concurrent BCR::ABL1 translocation, and JAK2 and SF3B1 co-mutations with severe fibrosis: a case report

Abstract Introduction/Objective Myeloproliferative neoplasms (MPNs) arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of MPNs is based on hematologic, histopathologic and molecular characteristics including the presence of BCR::ABL1 and JAK2 V617F. Methods/Case Report We present a 72-year-old male with a myeloid neoplasm and severe fibrosis, with concurrent BCR::ABL1 translocation, and co-mutations in JAK2 and SF3B1. Initially, the patient was diagnosed with anemia, thrombocytosis and folic acid deficiency and was prescribed supplemental folic acid. At follow up, normocytic anemia and thrombocytosis were seen. Bone marrow biopsy showed overtly fibrotic marrow with maturing trilineage hematopoiesis, markedly increased megakaryopoiesis and ring sideroblasts. Chromosome analysis and sequential GTG-fluorescence in situ hybridization (FISH) of metaphases using the dual-fusion three color probe BCR/ABL1- ASS1 revealed abnormal results. A t(9;22)(q34;q11.2) was detected along with an atypical FISH signal pattern with a single BCR::ABL1 fusion on the derivative chromosome 22 instead of the typical two fusions, resulting in loss of one BCR::ABL1 fusion signal including loss of the ASS1 on the derivative chromosome 9. Next-generation sequencing (NGS) analysis detected double driver mutations, JAK2 p. Val617Phe and SF3B1 p. Lys700Glu in the patient. JAK2 V617F mutation was further confirmed by real-time quantitative PCR (qPCR) with variant allele frequencies of 39.7%. Additionally, the patient was positive for BCR::ABL1 p190 fusion transcript (10%). The presence of JAK2 and SF3B1 co-mutations along with ring sideroblasts and the patient’s clinical presentation suggests the diagnosis of myelodysplastic/myeloproliferative neoplasm with thrombocytosis and SF3B1 mutation. Results (if a Case Study enter NA) NA Conclusion Although, the detection of t(9;22) by chromosome analysis is a diagnostic feature of chronic myeloid leukemia (CML), our case adds to the limited information on co-existence of BCR::ABL1 and JAK2 V617F with SF3B1 mutations in severe fibrosis. The frequency of co-occurrence, the temporal order of acquisition and clonal relationship of these alterations is poorly understood, and it is also unclear for this case since there is no prior bone marrow biopsy or diagnostic work up. Literature search of these rare cases show that some patients with similar findings progress to myelofibrosis as in this patient. It is possible that the presence of two mutated tyrosine kinase genes accelerates disease progression.

Physico-chemical properties and biological evaluation of graphene quantum dots for anticancer drug susceptibility

Graphene quantum dots (GQDs) possess unique optical and biocompatible properties, making them suitable candidates for biomedical and pharmaceutical applications. This study reports the hydrothermal synthesis of pristine-GQD and doped variants: Nitrogen-GQD and Sulfur-GQD. The materials underwent thorough characterization techniques such as UV–vis, fluorescence, XRD, FE-TEM/SEM, EDX, and Raman spectroscopy. The particle sizes of these GQDs range from 2 to 5 nm. We conducted a comprehensive study through MTT assays to evaluate the potential cytotoxic effect of GQD and the doped variants. This study demonstrated their synergistic interactions with an anti-cancer drug, methotrexate (MTX), and also improvement of cytocompatibility in the presence of folic acid (FA). Systematic MD simulations revealed a compacting effect on the dynamic behavior of GQD and its variants in the presence of drugs. Fluorescence spectroscopy and computational modeling suggest non-intercalative surface interactions between GQDs and the drugs. The cytotoxic activity of pristine GQD on HeLa cervical cancer cells is higher than that of N-GQD and S-GQD. When treated with GQD-IC50–MTX-IC50, only 5.6 % of HeLa cells remained viable. The doped variants exhibited bio-compatibility when tested on normal HEK cell lines. Overall, this study emphasizes the potential of GQDs for targeted cancer therapy through an interdisciplinary approach involving material characterization, computational modeling, and biological assays.

Routine uptake of prenatal iron-folic acid supplementation and associated factors among pregnant women in peri-urban areas of Dodoma City, Tanzania: a cross-sectional study

BackgroundThe physiological requirements for iron and folic acid in pregnancy are a significant challenge to achieve through normal dietary intake, especially in low resource settings. The World Health Organization recommends daily oral iron and folic acid supplementation (IFAS) to prevent maternal anaemia and related adverse effects in community settings where the prevalence of anaemia during pregnancy is > 40%. The objective of this study was to assess the routine uptake of prenatal iron-folic acid supplementation and associated factors among pregnant women at peri-urban areas of Dodoma City, Tanzania.MethodsA cross-sectional study was conducted in peri-urban areas. Data was collected through face-to-face interviews and review of records from maternal clinic card (RCH 4 card). Routine uptake of iron-folic acid supplementation was defined as pregnant woman who reported taking iron-folic acid supplements at least once within the past seven days prior to data collection. Frequency and percentage were used to report respondents’ characteristics and uptake of prenatal iron-folic acid supplementation. Chi-square test and logistic regression were conducted to determine the relationship and association of routine uptake of iron-folic acid supplementation with respondents’ characteristics.ResultsThe total respondents were 452. Overall routine uptake of iron-folic acid supplementation was 35.6% (161). The majority of the respondents (66.5%) initiated iron-folic acid supplementation during the second trimester of pregnancy. Most of the respondents (86.3%) obtained IFA supplements at the health centers where they were receiving antenatal care. The prevalence of routine uptake of iron-folic acid supplementation was significantly higher among women in the third trimester of pregnancy (54.9%), those with more than a five-year interval since last pregnancy (40.6%), those with at least four antenatal care (ANC) visits (73.7%) and women who had undergone haemoglobin testing in the current pregnancy (63.0%). Factors associated with routine uptake of iron-folic acid supplementation were; frequency of ANC visits (AOR = 1.69) and haemoglobin testing (AOR = 3.02).ConclusionApproximately one third of the pregnant women took iron-folic acid supplementation at least once a week. The current frequency for intake of iron-folic acid supplementation can be described as intermittent. This practise is unacceptable for prevention of maternal anaemia and associated adverse pregnant outcomes. Frequency of ANC visits and haemoglobin testing during pregnancy were found to be associated with routine uptake of iron-folic acid supplements. Stakeholders are urged to consider novel systems for provision of prenatal IFAS in community settings with limited access to health-care professionals to ensure a timely and continuous supply of supplements.

Perfluorodecanethiol-Functionalized Silver Nanoparticles on Polyester Films as High-Performance Surface-Enhanced Raman Spectroscopy Substrates.

The insufficient capabilities of current surface-enhanced Raman scattering (SERS) substrates in enriching dilute analytes from complex media severely restrict detection sensitivity, hampering practical applications. To meet this demand, in this study, a novel super hydrophobic membrane that can be directly prepared on a large scale based on the silver nanoparticles (AgNPs) functioning with perfluorodecanethiol (PFDT) is fabricated and evaluated as an SERS substrate. Firstly, polyester (PET) films modified with sodium chloride were proven to be capable of loading AgNPs, and the sizes of AgNPs were investigated. In addition, the PFDT concentration and reaction time for functionalizing the surface of AgNPs have been optimized. The relationship between the hydrophobic properties of the film and its SERS performance was then studied. The PET@Ag-PFDT film demonstrates two orders of magnitude superior SERS performance than the unmodified PET@Ag substrate, with a detection limit of folic acid approaching 5 × 10-10 M.

A Case Report on Methotrexate Overdose Induced Pancytopenia and Toxic Epidermal Necrolysis

Methotrexate is commonly used for autoimmune diseases including rheumatoid arthritis, psoriasis, sarcoidosis, and eczema due to its anti-inflammatory and immunosuppressive effect. The following report describes the case of a 48-year-old female presenting with complaints of fever, erythematous rash and blister over upper limb and oral hemorrhagic mucositis. She was previously diagnosed with rheumatoid arthritis and left sided poliomyelitis and was on methotrexate 15 mg weekly, but the patient had taken it daily resulting in toxicity. she was hospitalized, treated with folic acid, injection leucovorin & inj. filgrastim. Our case highlights the importance of counselling to ensure adherence to the correct methotrexate treatment regimen to prevent toxicity and its side effect.

Lactobacillus Eats Amyloid Plaque and Post-Biotically Attenuates Senescence Due to Repeat Expansion Disorder and Alzheimer's Disease.

Patients with Alzheimer's disease and related dementia (ADRD) are faced with a formidable challenge of focal amyloid deposits and cerebral amyloid angiopathy (CAA). The treatment of amyloid deposits in ADRD by targeting only oxidative stress, inflammation and hyperlipidemia has not yielded significant positive clinical outcomes. The chronic high-fat diet (HFD), or gut dysbiosis, is one of the major contributors of ADRD in part by disrupted transport, epigenetic DNMT1 and the folate 1-carbon metabolism (FOCM) cycle, i.e., rhythmic methylation/de-methylation on DNA, an active part of epigenetic memory during genes turning off and on by the gene writer (DNMT1) and eraser (TET2/FTO) and the transsulfuration pathway by mitochondrial 3-mercaptopyruvate sulfur transferase (3MST)-producing H2S. The repeat CAG expansion and m6A disorder causes senescence and AD. We aim to target the paradigm-shift pathway of the gut-brain microbiome axis that selectively inhibits amyloid deposits and increases mitochondrial transsulfuration and H2S. We have observed an increase in DNMT1 and decreased FTO levels in the cortex of the brain of AD mice. Interestingly, we also observed that probiotic lactobacillus-producing post-biotic folate and lactone/ketone effectively prevented FOCM-associated gut dysbiosis and amyloid deposits. The s-adenosine-methionine (SAM) transporter (SLC25A) was increased by hyperhomocysteinemia (HHcy). Thus, we hypothesize that chronic gut dysbiosis induces SLC25A, the gene writer, and HHcy, and decreases the gene eraser, leading to a decrease in SLC7A and mitochondrial transsulfuration H2S production and bioenergetics. Lactobacillus engulfs lipids/cholesterol and a tri-directional post-biotic, folic acid (an antioxidant and inhibitor of beta amyloid deposits; reduces Hcy levels), and the lactate ketone body (fuel for mitochondria) producer increases SLC7A and H2S (an antioxidant, potent vasodilator and neurotransmitter gas) production and inhibits amyloid deposits. Therefore, it is important to discuss whether lactobacillus downregulates SLC25A and DNMT1 and upregulates TET2/FTO, inhibiting β-amyloid deposits by lowering homocysteine. It is also important to discuss whether lactobacillus upregulates SLC7A and inhibits β-amyloid deposits by increasing the mitochondrial transsulfuration of H2S production.

COL8A2 activation enhances function of corneal endothelial cells through HIPPO signaling/mitochondria pathway

Corneal endothelial cells (CECs) are essential for maintaining corneal transparency and hydration through their barrier and pump functions. The COL8A2 gene encodes a component of the extracellular matrix of the cornea, which is crucial for the normal functioning of these cells. Mutations in COL8A2 are linked to corneal dystrophies, emphasizing the gene's importance in corneal health. The purpose of this research is to explore the effects of COL8A2 activation within CECs, to understand its contribution to cellular behavior and health. COL8A2 CRISPR/dCas9 activation system (aCOL8A2) was used to activate the COL8A2. In rats, wound healing and mitochondrial function were assessed after COL8A2 activation. As a result, aCOL8A2 promoted wound healing of rat corneal endothelium by increasing mitochondrial membrane potential. In cultured human CECs, proteomic analysis was performed to screen and identify the differential protein profiles between control and aCOL8A2 cells. Western blot was used to validate the differential proteins from both cells. Mitochondrial function and intracellular distribution were assessed by measuring ATP production and mitochondrial membrane potential. In cultured human CECs, aCOL8A2 increased COL8A2 and phospho-YAP levels. Transendothelial electrical resistance (TEER) was increased and actin cytoskeleton was attenuated by aCOL8A2. Gene ontology analysis revealed that the proteins were mainly involved in the regulation of folate biosynthesis, ECM-receptor interaction, cell differentiation, NADP activity and cytoskeleton. ATP production was increased, mitochondrial membrane potential was polarized and mitochondrial distribution was widespread in the aCOL8A2 group. In conclusion, aCOL8A2 induces a regulatory cascade affecting mitochondrial positioning and efficiency, mediated by alterations in the cytoskeletal architecture and the YAP signaling pathway. This sequence of events serves to bolster the functional capacities of corneal endothelial cells, including their pump and barrier functions, essential for corneal health and transparency.

Synergistic enhancement of chemical and electromagnetic effects in a Ti3C2Tx/AgNPs two-dimensional SERS substrate for ultra-sensitive detection

BackgroundIt is well established that surface-enhanced Raman scattering (SERS) is one of the most commonly used spectral analysis techniques in real-world applications, including chemical and biological sensing, analytical detection, and even forensics. It offers high sensitivity, high resistance to solvents, photobleaching, and limited spectrum bands. In general, SERS is caused by two mechanisms, the electromagnetic enhancement mechanism (EM) and the chemical enhancement mechanism (CM), although the exact mechanism is not yet known. For increased sensitivity, a SERS substrate based on EM coupled with CM is essential. ResultsUsing electrostatic self-assembly, we fabricated many homogeneous hot spots for the substrate by evenly mixing positive charge Ag nanoparticles (AgNPs) with negative charge Ti3C2Tx. In addition, there is a clearly enhanced effect due to the high affinity between the tested molecule and Ti3C2Tx, which facilitates molecule-to-molecule charge transfer. After successfully preparing the Ti3C2Tx/AgNPs substrate, the R6G dye molecule was used to investigate its SERS activity. According to the results, the substrate can reach an enhancement factor of 3.8 × 108. Furthermore, it has been demonstrated that the coupling effect between EM and CM is the main reason for the excellent performance of the Ti3C2Tx/AgNPs composite substrate. Based upon the results of detecting the two biomarkers, adenosine triphosphate and folic acid, the detection limits were determined to be 4.27 × 10−9 M and 7.26 × 10−13 M, respectively. Significance and noveltyTwo-dimensional metal carbide Ti3C2Tx material can be used to obtain CM in surface Raman scattering. It has been demonstrated that the combination of CM and EM with nano-precious metals can produce an extremely sensitive SERS substrate that is dependable and stable. Additionally, the Ti3C2Tx/AgNPs study offers a novel perspective for the advancement of the SERS coupling mechanism in addition to providing direction for realistic detection.